Weight loss drugs and surgery improve fat-to-muscle ratio in obesity

Both the new weight loss drugs and bariatric surgery improve body composition in patients with obesity by inducing a moderate loss of fat-free mass (including lean muscle) along with a substantial reduction in fat, researchers at Vanderbilt Health have found.

Weight loss study team: From left, Danxia Yu, PhD, Zicheng Wang, MS, Lei Wang, PhD, and Jason Samuels, MD, are co-authors of a paper evaluating body composition changes after bariatric surgery or treatment with the new weight loss drugs (Credit: Photo by Donn Jones).

This is important because while a higher percentage of fat mass (FM) is associated with an elevated risk of mortality from obesity-related diseases, including adverse cardiovascular events, a higher percentage of fat-free mass (FFM) is protective against mortality. 

However, additional studies are needed to determine how FM and FFM change after bariatric surgery or treatment with current GLP-1 receptor agonist drugs in real-world clinical settings, the researchers stated.

The study was led by Dr Danxia Yu, associate professor of Medicine in the Division of Epidemiology, and Dr Jason Samuels, assistant professor of Surgery.  Their retrospective study analysed the electronic health records of 1,257 patients ages 18 to 65 who underwent bariatric surgery at Vanderbilt Health from 2017 to 2022, and 1,809 patients treated with the drugs semaglutide or tirzepatide from 2018 to 2023. The study excluded those with a history of end-stage renal disease or congestive heart failure. 

Body composition was quantified by bioelectrical impedance analysis, which estimates FM and FFM according to individual characteristics including height, weight, age, race, gender, history of diabetes and GLP-1 treatment duration.

The researchers found that, over 24 months, both medical and surgical weight loss approaches led to significant reductions in FM, modest reductions in FFM, and increases in the FFM/FM ratio, reflecting improved body composition. Male patients showed better long-term preservation of FFM than female patients.

Overall, the adjusted mean relative FM reductions in the surgery group were 42.4% (95% CI, 41.5%-43.2%) at 6 months, 49.7% (95% CI, 48.8%-50.6%) at 12 months, and 49.7% (95% CI, 47.8%-51.5%) at 24 months; reductions in the GLP-1RA group were 10.3% (95% CI, 9.5%-11.0%) at 6 months, 17.3% (95% CI, 16.5%-18.1%) at 12 months, and 18.0% (95% CI, 16.4%-19.7%) at 12 months.

Adjusted mean relative FFM reductions in the surgery group were 7.8% (95% CI, 7.2%-8.4%) at 6 months, 10.6% (95% CI, 10.0%-11.2%) at 12 months, and 11.7% (95% CI, 10.4%-12.9%) at 24 months; reductions in the GLP-1RA group were 1.8% (95% CI, 1.3%-2.4%) at 6 months, 3.0% (95% CI, 2.4%-3.5%) at 12 months, and 3.3% (95% CI, 2.1%-4.4%) at 24 months.

FFM to FM ratios increased significantly in both groups, with surgical patients maintaining a higher ratio throughout: the FFM to FM ratios in the surgery group were 1.8 (95% CI, 1.8-1.8) at 6 months, 2.1 (95% CI, 2.1-2.1) at 12 months, and 2.0 (95% CI, 2.0-2.1) at 24 months; the FFM to FM ratios in the GLP-1RA group were 1.4 (95% CI, 1.4-1.4) at 6 months, 1.5 (95% CI, 1.4-1.5) at 12 months, and 1.5 (95% CI, 1.5-1.6) at 24 months.

Similar trends were observed in stratified analyses by sex, race, baseline BMI, baseline diabetes status, and GLP-1RA treatment duration, although men showed better FFM preservation than women, especially after GLP-1RA treatment.

The study was supported in part by National Institutes of Health grants R01DK126721 and R01CA275864.

The findings were reported in the paper, ‘Body Composition Changes After Bariatric Surgery or Treatment With GLP-1 Receptor Agonists’, published in JAMA Network Open. To access this paper, please click here